Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Evacuation plan of the city of almere: Simulating the impact of driving behavior on evacuation clearance time

The evacuation clearance time is one of the key indicators in an evacuation plan and is determined by the expected behavior of the endangered residents and roadway network characteristics. The city of Almere has developed an evacuation plan in case of the emergency of a flooding, but assumes a normal driving behavior of the evacuees. In this paper a microscopic S-Paramics simulation framework in an evacuation condition is set up to assess the impact of variations in driving behavior on the evacuation clearance time. Different scenarios in terms of acceleration rate, maximum speed, mean headway and minimum gap distance have been developed. The results show that increases in acceleration rate and in maximum speed do not have a significant impact on the evacuation clearance time. It is also found that a reduction both in mean headway and in minimum gap significantly reduce the evacuation time. Therefore, it is very important to consider the driving behavior in an evacuation condition for an evacuation plan.Transport & PlanningCivil Engineering and Geoscience

Rising temperatures increase importance of oceanic evaporation as a source for continental precipitation

Understanding vulnerabilities of continental precipitation to changing climatic conditions is of critical importance to society at large. Terrestrial precipitation is fed by moisture originating as evaporation from oceans and from recycling of water evaporated from continental sources. In this study, continental precipitation and evaporation recycling processes in the Earth system model GFDL-ESM2G are shown to be consistent with estimates from two different reanalysis products. The GFDL-ESM2G simulations of historical and future climate also show that values of continental moisture recycling ratios were systematically higher in the past and will be lower in the future. Global mean recycling ratios decrease 2%–3% with each degree of temperature increase, indicating the increased importance of oceanic evaporation for continental precipitation. Theoretical arguments for recycling changes stem from increasing atmospheric temperatures and evaporative demand that drive increases in evaporation over oceans that are more rapid than those over land as a result of terrestrial soil moisture limitations. Simulated recycling changes are demonstrated to be consistent with these theoretical arguments. A simple prototype describing this theory effectively captures the zonal mean behavior of GFDL-ESM2G. Implications of such behavior are particularly serious in rain-fed agricultural regions where crop yields will become increasingly soil moisture limited.Water Resource

Analyzing cell-type-specific dynamics of metabolism in kidney repair

A common drawback of metabolic analyses of complex biological samples is the inability to consider cell-to-cell heterogeneity in the context of an organ or tissue. To overcome this limitation, we present an advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) combined with isotope tracing. This method allows mapping of cell-type-specific dynamic changes in central carbon metabolism in the context of a complex heterogeneous tissue architecture, such as the kidney. Combined with multiplexed immunofluorescence staining, this method can detect metabolic changes and nutrient partitioning in targeted cell types, as demonstrated in a bilateral renal ischemia–reperfusion injury (bIRI) experimental model. Our approach enables us to identify region-specific metabolic perturbations associated with the lesion and throughout recovery, including unexpected metabolic anomalies in cells with an apparently normal phenotype in the recovery phase. These findings may be relevant to an understanding of the homeostatic capacity of the kidney microenvironment. In sum, this method allows us to achieve resolution at the single-cell level in situ and hence to interpret cell-type-specific metabolic dynamics in the context of structure and metabolism of neighboring cells.Pattern Recognition and Bioinformatic